This application requests funds for the purchase of a modern, flexible and state-of-the-art Jeol transmission electron microscope (TEM) to replace an aging TEM in the Central Electron Microscopic Laboratory in the Department of Pathology. The requirements for the TEM work of NIH-funded investigators cannot be met with the present available equipment which does not have a goniometer stage, scanning transmission attachment, or the ability to perform at accelerating voltages higher than 60 kV. A significant percentage of laboratory personnel's time is devoted to maintenance and repair of the microscopes, and a substantial wastage of photographic film occurs due to their design failings. The central laboratory for which the TEM is requested is a well equipped laboratory for the performance of conventional electron microscopy, and its personnel are extensively trained and highly skilled in the techniques of electron microscopy. Even if the age-related failures of the TEM did not exist, the limitations of the present TEM would constitute a bottleneck with respect to the research and service functions of the laboratory. This laboratory is, in fact, the only central facility in the Medical Center which has a scanning electron microscope, Kevex analytical ED system and freeze-fracture unit and serves a large number of NIH-funded investigators. This is evident from a number of published papers resulting from the existence of this facility. The lack of the requested TEM will severely limit the productivity and quality of work required by the user group and many other NIH-funded investigators. Finally, provision of this microscope can also serve as an adjunct to the analytical microscopy.